Angelo Manfredi
Angelo Manfredi
affiliation: Università Vita-Salute San Raffaele
research area(s): Stem Cells And Regenerative Medicine, Immunity And Infection
Course: Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele
1989: Degree cum laude in Allergy and Clinical Immunology, University of Milano.
1985: Member of the Italian College of Physicians and Surgeons.
1985: M.D. cum laude, University of Milano.
1979: High school diploma with maximum quotation marks (60/60), Classical Lyceum "Berchet" Milano.

2003-date: Associate Professor of Internal Medicine, San Raffaele Vita-Salute University, Milano
2002-date: Head of the Unit of Autoimmunity and Vascular Inflammation, Istituto Scientifico S. Raffaele, Milano
1998-date: Member and group leader, CIGTP, Istituto Scientifico H S.Raffaele, Milano.
1996: Visiting Scientist, Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Marseille, France.
1992: Visiting Scientist, Department of Biochemistry and Department of Pharmacology, University of Minnesota.
1992-date: Investigator, Istituto Scientifico H S. Raffaele, Milano, Second Department of Medicine and Laboratory of Immunology.
1988-1991: Post-doctoral Associate, University of Minnesota, St. Paul 55108, USA.
1986-1987: Intern, Second Department of Internal Medicine and Laboratory of Immunology, Istituto Scientifico H S.Raffaele, Milano.

1989-91: Research Post-Doctoral fellowship of the Muscular Dystrophy Association of USA.
1986-1988: Recipient of the "R. Mattioli" award.

Prof. Manfredi is a member of the Società Italiana di Allergologia, Immunologia e Immunologia Clinica. He is a member of the editorial board of Clinical & Experimental Immunology, and of The Open Rheumatology Journal and of the board of reviewers of: American Journal of Pathology, Annals of Rheumatic Diseases, Apoptosis, Arthritis & Rheumatism, Arthritis Care & Research, Autoimmunity, Biochemistry, Blood, British Journal of Cancer, British Journal of Pharmacology, Cancer Research, Cell Death & Differentiation, Clinical & Experimental Immunology, Clinical Cancer Research, Cytometry, Experimental Cell Research, European Journal of Histochemistry, European Journal of Immunology, Human Gene Therapy, Immunology, International Journal of Cancer, Journal of Autoimmunity, Journal of Biological Chemistry, Journal of Immunology, Journal of Immunological Methods, Journal of Infectious Diseases, Journal of Investigative Dermatology, Journal of Leukocyte Biology, Journal of Neurochemistry, Journal of Neuroimmunology, Molecular Cancer Therapeutics, Nature Medicine, Reproductive Sciences, Signal Transduction, Trends in Immunology.

Prof. Manfredi is a consultant and a grant reviewer for:

Ministero dell'Istruzione, dell'Universita' e della Ricerca (MIUR), Istituto Superiore di Sanità, Ministero della Salute, for the Comitato di Indirizzo per la Valutazione della Ricerca (CIVR), Università degli studi di Padova, Università degli studi di Verona, Arthritis Research Campaign (U.K.), Association for International Cancer Research (U.K.), MRC (U.K.), Welcome Trust (U.K.), French National Cancer Institute (INCa, France), United States-Israel Binational Science Foundation (Jerusalem-Bethesda), EMBO fellowship organization, Austrian Science Fund (FWF, Austria), The Icelandic Research Fund (IRF, Reykjavìk, Iceland), the Research Fund for the Control of Infectious Disease (Hong Kong), the Reumafonds (Dutch Arthritis Association).

Papers of Prof. Manfredi have been quoted as "papers of outstanding interest" and "papers of special interest" of the Bibliography of the Current World Literature, Current Opinion in Immunology (1993, 1999, 2000, 2005, 2006, 2008), Current Opinion in Microbiology (1999), Current Opinion in Nephrology and Hypertension (1999 and 2007), Current Opinion in Rheumatology (2000).

1. Innate response to primary inflammatory signals in the origin of systemic autoimmunity

2. Pathways regulating the clearance of apoptotic cells and particulate substrates in self-sustaining vascular inflammation

Invited Reviews and Commentaries

1. Manfredi AA, Rovere-Querini P. The mitochondrion - A Trojan horse that kicks off inflammation? New England Journal of Medicine, 2010; 362, 2132-2134.
2. Munoz L, Lauber L, Schiller M, Manfredi AA, Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nature Rev. Rheumatology, 2010, 6:280-289
3. Manfredi AA, Rovere-Querini P, Maugeri N. Dangerous connections: neutrophils and the phagocytic clearance of activated platelets. Curr Opin Hematol. 2010, 17:3-8.
4. Bianchi ME, Manfredi AA. Immunology. Dangers in and out. Science. 2009; 323 (5922) :1683-4.
5. Manfredi AA, Capobianco A, Bianchi ME, Rovere-Querini P. Regulation of dendritic- and T-cell fate by injury-associated endogenous signals. Crit Rev Immunol 2009;29(1):69-86.
6. Maugeri N, Rovere-Querini P, Baldini M, Sabbadini MG, Manfredi AA. Translational mini-review series on immunology of vascular disease: mechanisms of vascular inflammation and remodelling in systemic vasculitis. Clin Exp Immunol. 2009;156(3):395-404.
7. Clementi E, Manfredi AA. The immune system facing injured tissues and stem cells: more of a healer or a fighter? Pharmacol Res. 2008;58(2):87. Editorial.
8. Manfredi AA, Rovere-Querini P, Bottazzi B, Garlanda C, Mantovani A. Pentraxins, humoral innate immunity and tissue injury. Curr Opin Immunol. 2008 Oct;20(5):538-44.
9. Bianchi ME, Manfredi AA. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev. 2007 Dec;220(1):35-46.

Original Research Articles
1. Maugeri N, Malato S, Femia EA, Pugliano M, Campana L, Lunghi F, Rovere-Querini P, Lussana F, Podda GM, Cattaneo M, Ciceri F, Manfredi AA. Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia. Blood. 2011 in press
2. Maugeri N, Rovere-Querini P, Slavich M, Coppi G, Doni A, Bottazzi B, Garlanda C, Cianflone D, Maseri A, Mantovani A, Manfredi AA. Early and Transient Release of Leukocyte Pentraxin 3 during Acute Myocardial Infarction.J Immunol. 2011 Jul 15;187(2):970-9.
3. Maroso M, Balosso S, Ravizza T, Liu J, Aronica E, Iyer AM, Rossetti C, Molteni M, Manfredi AA, Bianchi ME, Vezzani A. A causative role of Toll-Like Receptor 4 (TLR4) activation by High Mobility Group Box 1 (HMGB1) protein in ictogenesis. Nature Medicine, 2010, 16:413-419
4.Pluchino S, Zanotti L, Brambilla E, Rovere-Querini P, Capobianco A, Alfaro-Cervello C, Salani G, Cossetti C, Borsellino G, Battistini L, Ponzoni M, Doglioni C, Garcia-Verdugo JM, Comi G, Manfredi AA, Martino G. Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function. PLoS One. 2009 ;4(6):e5959.
5. Maugeri N, Rovere-Querini P, Evangelista V, Covino C, Capobianco A, Bertilaccio MT, Piccoli A, Totani L, Cianflone D, Maseri A, Manfredi AA Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and {beta}2 integrin-dependent cell clearance program. Blood. 2009 21;113(21):5254-65.
6. Di Comite G, Rossi CM, Marinosci A, Lolmede K, Baldissera E, Aiello P, Mueller RB, Herrmann M, Voll RE, Rovere-Querini P, Sabbadini MG, Corti A, Manfredi AA. Circulating chromogranin A reveals extra-articular involvement in patients with rheumatoid arthritis and curbs TNF-alpha-elicited endothelial activation. J Leukoc Biol. 2009;85(1):81-7.
7. Di Comite G, Previtali P, Rossi CM, Dell'Antonio G, Rovere-Querini P, Praderio L, Dagna L, Corti A, Doglioni C, Maseri A, Sabbadini MG, Manfredi AA. High blood levels of chromogranin A in giant cell arteritis identify patients refractory to corticosteroid treatment. Ann Rheum Dis. 2009;68(2):293-5.
8. Manfredi AA, Capobianco A, Esposito A, De Cobelli F, Canu T, Monno A, Sanvito F, Raucci A, Doglioni C, Nawroth PP, Bierhaus A, Rovere-Querini P, Del Maschio A, Maturing Dendritic Cells Depend on RAGE for In Vivo Homing to Lymph Nodes. J Immunol 2008 180(4):2270-5.
9. Urbonaviciute V, Fürnrohr BG, Meister S, Munoz L, Heyder P, De Marchis F, Bianchi ME, Kirschning C, Wagner H, Manfredi AA, Kalden JR, Schett G, Rovere-Querini P, Herrmann M, Voll RE. Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med. 2008 22;205(13):3007-18.

Project Title:
Molecular determinants of vascular inflammation.
Vessel walls inflammation has dramatic consequences. The initiating or precipitating event is in most cases unknown, and a self-sustaining circuit attracts and activates inflammatory leukocytes in the wall of vessels. Humoral innate immunity, in particular injury-associated signals and acute phase proteins, influence the activation of circulating leukocytes, platelets and endothelial cells, which in turn is involved both in thrombus formation/stabilization and in vessel wall remodelling. The general goal of this project is to identify the role of key molecules involved in the early phases of atherothrombosis in murine experimental models. Specific aims will be:
- to verify the role of molecules that we expect to play a relevant role, injecting platelets in Mac-1- deficient mice, Src family kinases Hck and Fgr double knock-out mice or Pyk2-deficient mice.
- to characterize the hierarchy of events after the in vivo recognition of platelet P-selectin by the P-selectin glycoprotein ligand-1 (PSGL-1) counter-receptor expressed on the surface of granulocytes and monocytes, with attention to the role of the leukocyte integrin alphaMbeta2 (Mac-1) transactivation for leukocyte recruitment, establishment of persistent vascular inflammation and initiation and propagation of arterial thrombi
- to identify the possible involvement of intracellular signals capable to regulate leukocyte activation, with specific attention to the role of the prototypical damage associated molecular pattern HMGB1 and of mitochondrial constituents.